184 research outputs found

    Variation in tospovirus transmission between populations of Frankliniella occidentalis (Thysanoptera: Thripidae)

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    Fourteen populations of the western flower thrips Frankliniella occidentalisPergande, originating from different hosts and countries in Asia, Europe, North America and New Zealand, were analysed for their competency and efficiency to transmit tomato spotted wilt virus (TSWV). All populations acquired and subsequently transmitted the virus, and were thus competent to transmit. They show marked differences in their efficiency, expressed as the percentage of transmitting adults. Efficiencies varied from 18 or a F. occidentalis population from the USA (US2) to 75␈r a population from Israel (IS2). The differences between populations were not affected by the amount of virus ingested or by the host plant used. However, the tospovirus species studied and age at which the larvae acquired the virus affected the efficiency to transmit. First instar larvae of the NL3 population from The Netherlands were able to acquire tomato spotted wilt virus, whereas second instar larvae failed to do so. However, both instars of this population acquired impatiens necrotic spot virus (INSV), another tospovirus. This and tomato spotted wilt virus were both acquired by both larval stages of the populations IS2 and US2, although their ability to acquire virus decreased with their age. Hence, it is likely that, in general, both instar larvae of most F. occidentalis populations are competent to acquire both tospoviruses. These results show that large differences exist in the efficiency by which tomato spotted wilt is transmitted by the various F. occidentalis populations and that the ability to acquire tospovirus decreases with the age of the larva

    Non-uniform recovery of left ventricular transmural mechanics in ST-segment elevation myocardial infarction

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    <p>Abstract</p> <p>Background</p> <p>After a transient ischemic episode, the subendocardial region is more severely injured than outer subepicardial layers and may regain a proportionately greater degree of mechanical function in the longitudinal direction. We sought to explore left ventricular (LV) transmural mechanics in patients with ST-segment elevation myocardial infarction (STEMI) for determining the mechanism underlying recovery of global LV function after primary percutaneous coronary intervention (PCI).</p> <p>Methods</p> <p>A total of 42 patients (62 ± 11 years old, 71% male) with a first STEMI underwent serial assessments of LV longitudinal, circumferential and radial strains (LS, CS and RS) by selective tracking of subendocardial and subepicardial regions within 48 hours and a median of 5 months after PCI. LV mechanical parameters were compared with sixteen age and gender matched normal controls.</p> <p>Results</p> <p>In comparison with controls, endocardial and epicardial LS were markedly attenuated at 48 hours following PCI (P < 0.001). An improvement in LV ejection fraction (EF > 5%) following PCI was seen in 24 (57%) patients and was associated with improvement in endocardial and epicardial LS (P < 0.001 and P = 0.003, respectively) and endocardial CS (P = 0.01). Radial strain and wall motion score index, however, remained persistently abnormal. The change in endocardial LS (OR 1.2, 95% CI 1.03 to 1.42, P = 0.01) and the change in epicardial LS (OR 1.2, 95% 1.03 to 1.46, P = 0.02) were significantly associated with the improvement in LVEF, independent of the location of STEMI and the presence of underlying multivessel disease.</p> <p>Conclusions</p> <p>In patients with STEMI treated by PCI, the recovery of LV subendocardial shortening strain seen in the longitudinal direction underlies the improvement in LV global function despite persistent abnormalities in radial mechanics and wall motion score index.</p

    Participation in and attitude towards the national immunization program in the Netherlands: data from population-based questionnaires

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    Contains fulltext : 108971.pdf (publisher's version ) (Open Access)BACKGROUND: Knowledge about the determinants of participation and attitude towards the National Immunisation Program (NIP) may be helpful in tailoring information campaigns for this program. Our aim was to determine which factors were associated with nonparticipation in the NIP and which ones were associated with parents' intention to accept remaining vaccinations. Further, we analyzed possible changes in opinion on vaccination over a 10 year period. METHODS: We used questionnaire data from two independent, population-based, cross-sectional surveys performed in 1995-96 and 2006-07. For the 2006-07 survey, logistic regression modelling was used to evaluate what factors were associated with nonparticipation and with parents' intention to accept remaining vaccinations. We used multivariate multinomial logistic regression modelling to compare the results between the two surveys. RESULTS: Ninety-five percent of parents reported that they or their child (had) participated in the NIP. Similarly, 95% reported they intended to accept remaining vaccinations. Ethnicity, religion, income, educational level and anthroposophic beliefs were important determinants of nonparticipation in the NIP. Parental concerns that played a role in whether or not they would accept remaining vaccinations included safety of vaccinations, maximum number of injections, whether vaccinations protect the health of one's child and whether vaccinating healthy children is necessary. Although about 90% reported their opinion towards vaccination had not changed, a larger proportion of participants reported to be less inclined to accept vaccination in 2006-07 than in 1995-96. CONCLUSION: Most participants had a positive attitude towards vaccination, although some had doubts. Groups with a lower income or educational level or of non-Western descent participated less in the NIP than those with a high income or educational level or indigenous Dutch and have been less well identified previously. Particular attention ought to be given to these groups as they contribute in large measure to the rate of nonparticipation in the NIP, i.e., to a greater extent than well-known vaccine refusers such as specific religious groups and anthroposophics. Our finding that the proportion of the population inclined to accept vaccinations is smaller than it was 10 years ago highlights the need to increase knowledge about attitudes and beliefs regarding the NIP

    Identification of the Photoreceptor Transcriptional Co-Repressor SAMD11 as Novel Cause of Autosomal Recessive Retinitis Pigmentosa

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    Retinitis pigmentosa (RP), the most frequent form of inherited retinal dystrophy is characterized by progressive photoreceptor degeneration. Many genes have been implicated in RP development, but several others remain to be identified. Using a combination of homozygosity mapping, whole-exome and targeted next-generation sequencing, we found a novel homozygous nonsense mutation in SAMD11 in five individuals diagnosed with adult-onset RP from two unrelated consanguineous Spanish families. SAMD11 is ortholog to the mouse major retinal SAM domain (mr-s) protein that is implicated in CRX-mediated transcriptional regulation in the retina. Accordingly, protein-protein network analysis revealed a significant interaction of SAMD11 with CRX. Immunoblotting analysis confirmed strong expression of SAMD11 in human retina. Immunolocalization studies revealed SAMD11 was detected in the three nuclear layers of the human retina and interestingly differential expression between cone and rod photoreceptors was observed. Our study strongly implicates SAMD11 as novel cause of RP playing an important role in the pathogenesis of human degeneration of photoreceptors.This work was supported by several grants from the Spanish Centre for Biomedical Network Research on Rare Diseases (CIBERER)(06/07/0036), Instituto de Salud Carlos III (ISCIII, Spanish Ministry of Health)/FEDER, including FIS (PI013/00226) and RETICS (RD09/0076/00101 and RD12/0034/0010), Ministry of Economy and Competitiveness (MINECO), including FEDER (BFU2012-36845), and BIO2011-27069, Conselleria de EducaciĂł of the Valencia Community (PROMETEOII/2014/025), Spanish National Organization of the Blind (ONCE) and the Spanish Fighting Blindness Foundation (FUNDALUCE). M.C. was sponsored by the Miguel Servet Program for Researchers in the Spanish National Health Service (CP12/03256) and RSA by Sara Borrel Postdoctoral Program (CD12/00676), both from the ISCIII/FEDER. A.A-F. was sponsored by CIBERER, RPC is supported by FundaciĂłn Conchita RĂĄbago (FCR), L.C is sponsored by RETICS (RD12/0034/0010) from ISCIII and L.d.S. was supported by CAPES Foundation, Ministry of Education of Brazil

    Nuclear Receptor Rev-erb Alpha (Nr1d1) Functions in Concert with Nr2e3 to Regulate Transcriptional Networks in the Retina

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    The majority of diseases in the retina are caused by genetic mutations affecting the development and function of photoreceptor cells. The transcriptional networks directing these processes are regulated by genes such as nuclear hormone receptors. The nuclear hormone receptor gene Rev-erb alpha/Nr1d1 has been widely studied for its role in the circadian cycle and cell metabolism, however its role in the retina is unknown. In order to understand the role of Rev-erb alpha/Nr1d1 in the retina, we evaluated the effects of loss of Nr1d1 to the developing retina and its co-regulation with the photoreceptor-specific nuclear receptor gene Nr2e3 in the developing and mature retina. Knock-down of Nr1d1 expression in the developing retina results in pan-retinal spotting and reduced retinal function by electroretinogram. Our studies show that NR1D1 protein is co-expressed with NR2E3 in the outer neuroblastic layer of the developing mouse retina. In the adult retina, NR1D1 is expressed in the ganglion cell layer and is co-expressed with NR2E3 in the outer nuclear layer, within rods and cones. Several genes co-targeted by NR2E3 and NR1D1 were identified that include: Nr2c1, Recoverin, Rgr, Rarres2, Pde8a, and Nupr1. We examined the cyclic expression of Nr1d1 and Nr2e3 over a twenty-four hour period and observed that both nuclear receptors cycle in a similar manner. Taken together, these studies reveal a novel role for Nr1d1, in conjunction with its cofactor Nr2e3, in regulating transcriptional networks critical for photoreceptor development and function

    Electrical and Mechanical Ventricular Activation During Left Bundle Branch Block and Resynchronization

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    Cardiac resynchronization therapy (CRT) aims to treat selected heart failure patients suffering from conduction abnormalities with left bundle branch block (LBBB) as the culprit disease. LBBB remained largely underinvestigated until it became apparent that the amount of response to CRT was heterogeneous and that the therapy and underlying pathology were thus incompletely understood. In this review, current knowledge concerning activation in LBBB and during biventricular pacing will be explored and applied to current CRT practice, highlighting novel ways to better measure and treat the electrical substrate

    An exploratory qualitative assessment of factors influencing childhood vaccine providers' intention to recommend immunization in the Netherlands

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    <p>Abstract</p> <p>Background</p> <p>Under the Dutch national immunization program (NIP), childhood vaccination is not mandatory, but its recommendation by childhood vaccine providers (CVP) is important for maintaining high vaccination coverage. We therefore examined factors related to providers' intentions to recommend vaccinations to parents of young children.</p> <p>Methods</p> <p>We conducted four focus group discussions with nurses and physicians who provide vaccines to children 0-4 years old in diverse regions of the Netherlands. Three groups represented CVPs at child welfare centers (CWCs) serving the general population, with the fourth representing anthroposophical CWCs. Elements of the Theory of Planned Behaviour (TPB) were used to design the groups; thematic analysis was used to structure and analyze the dataset.</p> <p>Results</p> <p>Four main themes emerged, including 1) perceived responsibility: to promote vaccines and discuss pros and cons with parents (although this was usually not done if parents readily accepted the vaccination); 2) attitudes toward the NIP: mainly positive, but doubts as to NIP plans to vaccinate against diseases with a low perceived burden; 3) organizational factors: limited time and information can hamper discussions with parents; 4) relationship with parents: crucial and based mainly on communication to establish trust. Compared to CVPs at standard CWCs, the anthroposophical CWCs spent more time communicating and were more willing to adapt the NIP to individual cases.</p> <p>Conclusions</p> <p>Our qualitative assessment provides an overview of beliefs associated with providers' intention to recommend vaccinations. They were motivated to support the NIP, but their intentions to recommend vaccinations were affected by the perceived relevance of the vaccines, practical issues like limited time and by certain types of resistant parents. These results will inform future studies to test the magnitude and relative impact of these factors.</p

    Heterodimers of photoreceptor-specific nuclear receptor (PNR/NR2E3) and peroxisome proliferator-activated receptor (PPARÎł) are disrupted by retinal disease-associated mutations

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    Photoreceptor-specific nuclear receptor (PNR/NR2E3) and Tailless homolog (TLX/NR2E1) are human orthologs of the NR2E group, a subgroup of phylogenetically related members of the Nuclear Receptor (NR) superfamily of transcription factors. We assessed the ability of these NRs to form heterodimers with other members of the human NRs representing all major subgroups. The TLX ligand binding domain (LBD) did not appear to form homodimers or interact directly with any other NR tested. The PNR LBD was able to form homodimers, but also exhibited robust interactions with the LBDs of PPARÎł/NR1C3 and TRÎČ/NR1A2. The binding of PNR to PPARÎł was specific for this paralog, as no interaction was observed with the LBDs of PPARαNR1C1 or PPARÎŽNR1C2. In support of these findings, PPARÎł and PNR were found to be co-expressed in human retinal tissue extracts and could be co-immunoprecipitated as a native complex. Selected sequence variants in the PNR LBD associated with human retinopathies, or a mutation in the dimerization region of PPARÎł LBD associated with familial partial lipodystrophy type 3, were found to disrupt PNR/PPARÎł complex formation. Wild type PNR, but not a PNR309G mutant, was able to repress PPARÎł-mediated transcription in reporter assays. In summary our results reveal novel heterodimer interactions in the NR superfamily, suggesting previously unknown functional interactions of PNR with PPARÎł and TRÎČ that have potential importance in retinal development and disease
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